Early evaluation of subclinical cardiotoxicity in patients with lung cancer receiving immune checkpoint inhibitors by cardiovascular magnetic resonance: a prospective observational study

Abstract

Background: Few studies have focused on the subclinical cardiotoxicity of immune checkpoint inhibitors (ICIs) in cancer patients. This study aimed to evaluate the manifestations of subclinical cardiotoxicity of ICI therapy using cardiovascular magnetic resonance (CMR) and to explore whether CMR parameters can help predict cardiotoxicity at the early stage of ICI therapy.

Methods: A prospective, longitudinal study was conducted among patients with lung cancer. The patients were planned to undergo serial CMRs before (baseline), 3 weeks after (1st follow-up), and 3 months after (2nd follow-up) the initiation of ICI therapy, respectively. Patients with 3 CMRs were included in the analysis. Serial quantitative measurements based on CMR were compared using one-way repeated measures analysis of variance (RM-ANOVA). On the basis of cancer therapy-related cardiac dysfunction (CTRCD) observed at the second follow-up, patients were categorized into a CTRCD group and a non-CTRCD group. Baseline clinical and CMR parameters and the relative reduction of left ventricular global strain at the second follow-up was compared between the CTRCD group and the non-CTRCD group. Receiver operating characteristic (ROC) analysis was used to identify CTRCD that developed 3 months after ICI therapy.

Results: A total of 36 patients with 3 CMRs (60.7±9.2 years old, 77.8% male) were included in the analysis. Left ventricular-global radial strain (LV-GRS) decreased significantly at the second follow-up (37.9%±8.5% vs. 33.1%±1.0%; P=0.014), but left ventricular ejection fraction (LVEF) did not change significantly (51.5%±6.0% vs. 49.2%±6.5%; P>0.05). A total of 7 patients (19.4%) had developed CTRCD by the second follow-up. Baseline clinical and CMR parameters did not differ between the CTRCD group and the non-CTRCD group (P>0.05 for all). In the CTRCD group, the left ventricular-global circumferential strains (LV-GCSs) showed significant reductions at both the first and second follow-up (P=0.008 and 0.035, respectively), but the LVEF only showed a significant reduction at the second follow-up (P<0.001). The relative reduction of LV-GRS at the second follow-up was significantly higher in the CTRCD group than in the non-CTRCD group (29.8%±25.8% vs. 6.8%±20.4%; P=0.036) and was used to predict CTRCD developed at the 3-month timepoint after ICI therapy [area under the curve (AUC) =0.759; P=0.036].

Conclusions: In the early stage of ICI therapy, assessment of myocardial strain can be used to detect subclinical left ventricular systolic dysfunction in patients with lung cancer earlier than LVEF. The relative reduction of LV-GRS can be used to predict CTRCD 3 months after ICI therapy.

Keywords: Immune checkpoint inhibitor (ICI); cancer therapy-related cardiac dysfunction (CTRCD); cardiotoxicity; cardiovascular magnetic resonance (CMR); myocardial strain.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-41/coif). XZ is employed by Siemens Healthineers Ltd. The other authors have no conflicts of interest to declare.

2022 Quantitative Imaging in Medicine and Surgery. All rights reserved.

Figures

Figure 1

Strain analysis based on CMR tissue tracking. The LV strain is visualized by colored overlay on (A) short-axis and (B-D) 3 long-axis slices in the end-diastolic phase. The RV free wall strain is derived by contouring (E) 4-chamber long axis and (F) short-axis cine images. The contours of LA (orange line) and RA (blue line) at end-systolic and end-diastolic phases were automatically generated in (I,J) 2-chamber and (G,H) 4-chamber long-axis slices to calculate regional deformation, and the white lines connect the LA/RA apices and the midpoints of the mitral/tricuspid valves’ connecting lines, respectively. LA, left atrium; RA, right atrium; CMR, cardiovascular magnetic resonance; LV, left ventricle; RV, right ventricle.

Figure 2

Flow chart of our study cohort. CMR, cardiovascular magnetic resonance; ICI, immune checkpoint inhibitor.

Figure 3

A 66-year-old male patient was observed with pericardial effusion (arrows) on CMRs at 3 timepoints. Compared with (A) baseline, the pericardial effusion revealed a slight increase at (B) first follow-up and (C) second follow-up. CMR, cardiovascular magnetic resonance.

Figure 4

LVEF and global strain values at 3 timepoints in the CTRCD group and non-CTRCD group. *, P

Figure 5

Correlation between changes in LVEF values and changes in LV global strain values during follow-up. LV-GRS, left ventricular-global radial strain; LV-GCS, left ventricular-global circumferential strain; LV-GLS, left ventricular-global longitudinal strain; LVEF, left ventricular ejection fraction; LV, left ventricle.

Figure 6

Comparison of relative reductions of LVEF and global strains in the CTRCD group and non-CTRCD group 3 months after ICI therapy. *, P